Bile acids are important direct and indirect regulators of the secretion of appetite- and metabolism-regulating hormones from the gut and pancreas.
Bile acids are important direct and indirect regulators of the secretion of appetite- and metabolism-regulating hormones from the gut and pancreas.
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DOI：
10.1016/j.molmet.2018.03.007
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发表时间：
2018-05
影响因子：
8.1
通讯作者：
Holst JJ
中科院分区：
文献类型：
--
作者：
Kuhre RE;Wewer Albrechtsen NJ;Larsen O;Jepsen SL;Balk-Møller E;Andersen DB;Deacon CF;Schoonjans K;Reimann F;Gribble FM;Albrechtsen R;Hartmann B;Rosenkilde MM;Holst JJ
胆汁酸（BA）促进脂肪吸收，并可能在葡萄糖和代谢调节中发挥作用，刺激肠道激素的分泌。BA刺激肠道和胰腺分泌食欲和代谢调节激素的相对重要性和机制尚未得到充分描述，这是本研究的目的。在大鼠中研究了胆汁酸对肠道和胰腺激素分泌的影响，并与最广为人知的营养促分泌素：葡萄糖进行了比较。通过离体灌注大鼠和小鼠小肠和胰腺制备物研究了分泌的分子机制，并通过免疫组织化学、表达分析和药理学研究得到支持。胆汁酸不仅强烈刺激肠促胰岛素激素、葡萄糖依赖性促胰岛素肽（GIP）和胰高血糖素样肽-1（GLP-1）的分泌，而且刺激体内胰高血糖素和胰岛素的分泌，达到与葡萄糖刺激产生的水平相当的水平。GLP-1、神经降压素和肽YY（PYY）分泌的机制继发于肠吸收，并依赖于L细胞上基底外侧膜Takeda G蛋白受体5（TGR 5）受体的激活，效力顺序如下：石胆酸（LCA）>脱氧胆酸（DCA）>鹅脱氧胆酸（CDCA）>胆酸（CA）。因此，在TGR 5 KO小鼠中，BA不刺激灌流小肠分泌GLP-1和PYY，但在野生型同窝仔中刺激了强烈的反应。TGR 5在α细胞或β细胞上不表达，BA对灌注胰腺的胰高血糖素或胰岛素分泌没有直接影响。BA不仅被认为是脂肪乳化剂，而且通过激活基底侧肠道TGR 5作为食欲和代谢调节激素的重要调节剂。胆汁酸刺激肠道分泌代谢调节激素。胆汁酸刺激肠道激素分泌的程度与葡萄糖相似。基底外侧TGR 5受体的激活介导了这些反应。胆汁酸刺激胰高血糖素和胰岛素分泌，但只是间接的。胆汁酸应被视为血糖和代谢的重要调节剂。
Bile acids (BAs) facilitate fat absorption and may play a role in glucose and metabolism regulation, stimulating the secretion of gut hormones. The relative importance and mechanisms involved in BA-stimulated secretion of appetite and metabolism regulating hormones from the gut and pancreas is not well described and was the purpose of this study. The effects of bile acids on the secretion of gut and pancreatic hormones was studied in rats and compared to the most well described nutritional secretagogue: glucose. The molecular mechanisms that underlie the secretion was studied by isolated perfused rat and mouse small intestine and pancreas preparations and supported by immunohistochemistry, expression analysis, and pharmacological studies. Bile acids robustly stimulate secretion of not only the incretin hormones, glucose-dependent insulinotropic peptide (GIP), and glucagon-like peptide-1 (GLP-1), but also glucagon and insulin in vivo, to levels comparable to those resulting from glucose stimulation. The mechanisms of GLP-1, neurotensin, and peptide YY (PYY) secretion was secondary to intestinal absorption and depended on activation of basolateral membrane Takeda G-protein receptor 5 (TGR5) receptors on the L-cells in the following order of potency: Lithocholic acid (LCA) >Deoxycholicacid (DCA)>Chenodeoxycholicacid (CDCA)> Cholic acid (CA). Thus BAs did not stimulate secretion of GLP-1 and PYY from perfused small intestine in TGR5 KO mice but stimulated robust responses in wild type littermates. TGR5 is not expressed on α-cells or β-cells, and BAs had no direct effects on glucagon or insulin secretion from the perfused pancreas. BAs should be considered not only as fat emulsifiers but also as important regulators of appetite- and metabolism-regulating hormones by activation of basolateral intestinal TGR5. Bile acids stimulate the secretion of metabolism-regulating hormones from the gut. Bile acids stimulate secretion of gut hormones to a similar extent as glucose. Activation of basolateral TGR5 receptors mediates the responses. Bile acids stimulate glucagon and insulin secretion, but only indirectly. Bile acids should be regarded as important regulators of blood glucose and metabolism.
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影响因子：
3.5
作者：
Kuhre RE;Wewer Albrechtsen NJ;Deacon CF;Balk-Møller E;Rehfeld JF;Reimann F;Gribble FM;Holst JJ
通讯作者：
Holst JJ
DOI：
10.1016/j.bbrc.2005.01.139
发表时间：
2005-04-01
影响因子：
3.1
作者：
Katsuma, S;Hirasawa, A;Tsujimoto, G
通讯作者：
Tsujimoto, G
影响因子：
--
作者：
Kissow, Hannelouise;Hartmann, Bolette;Poulsen, Steen Seier
通讯作者：
Poulsen, Steen Seier
影响因子：
5.8
作者：
Hansen, M.;Scheltema, M. J.;Knop, F. K.
通讯作者：
Knop, F. K.
影响因子：
8.8
作者：
Albrechtsen, Nicolai J. Wewer;Albrechtsen, Reidar;Holst, Jens J.
通讯作者：
Holst, Jens J.